tbuckley/cabot-search huggingface dataset:
Abstract 10026: Augmentation of Slow Repolarizing Potassium Channel (I <sub>Ks</sub> ) Links Truncated Titin Mutations to Atrial Fibrillation
Authors: Olivia T Ly, Xinghang Jiang, Hanna Chen, Mahmud Arif Pavel, Grace Brown, Arvind Sridhar, David Tofovic, Richard Marszalek, Carlos Vanoye, Alfred L George, SALMAN KHETANI, Jalees Rehman, Ankur Saxena, Dawood Darbar
Journal: Circulation (2022)

Introduction: Rare titin-truncating variants ( TTN tv) are associated with early-onset atrial fibrillation (AF) but the pathogenic mechanisms and therapeutic implications remain unclear. To determine the function of a highly conserved immunoglobulin-like domain of the A-band of TTN , a region enriched in AF-associated variants, we employed CRISPR-Cas9-mediated deletion of 9 amino acids (Δ9) in human induced pluripotent stem cells and then derived atrial cardiomyocytes (hiPSC-aCMs) for electrophysiological (EP) analysis. Hypothesis: We hypothesized that the TTN -Δ9 mutation results in augmentation of the slow delayed rectifier potassium current (I Ks ) resulting in shortened action potential duration (APD). Methods: TTN -WT hiPSC-aCMs (healthy control) and TTN -Δ9 hiPSC-aCMs (isogenic mutant) were matured with metabolic conditioning, electrical stimulation, co-culture with atrial fibroblasts, and micropatterning. We used transmission electron microscopy (TEM) to assess sarcomeric defects, RNA-sequencing and RT-qPCR to assess molecular ion channel remodeling, and high throughput automated patch clamp and optical voltage mapping to assess the EP properties of TTN -Δ9 hiPSC-aCMs. We also performed targeted pharmacological inhibition of I Ks . Results: We showed that TTN -Δ9 hiPSC-aCMs displayed disrupted organization and myofibril assembly ( Fig. 1A-B ), upregulated voltage-gated potassium channel complexes and increased KCNQ1 expression ( Fig 1C-D ), and shortened APD ( Fig. 1E-F ). I Ks was significantly augmented in TTN -Δ9 hiPSC-aCMs ( Fig. 1G-H ). Infusion of the I Ks -specific blocker HMR-1556, and not I Kr blocker dofetilide, fully restored the shortened APD 90 and partially recovered defects in contractility in TTN -Δ9 hiPSC-aCMs compared to TTN -WT hiPSC-aCMs ( Fig. 1I-J ). Conclusion: Our findings suggest that augmentation of I Ks contributes to the pathogenic mechanism of TTN -mediated AF, pointing to I Ks as a potential therapeutic target.
Abstract 10081: The Moderator Role of Attitudes in the Relationship Between Knowledge and Self-Efficacy in Palliative Care Among Nurses: A Cross-Sectional, Correlational Study
Authors: Seongkum Heo, JinShil Kim, Minjeong An, jisun Yang, MIYEONG KIM, SeongHu Park, KyungAh Cho, Junghee J Kang
Journal: Circulation (2022)

Introduction: Provision of palliative care to patients with advanced chronic diseases or old populations is suboptimal, which results in unnecessary suffering of and burden to patients, caregivers, and society. Low self-efficacy in palliative care among nurses is a factor affecting suboptimal utilization of palliative care. Poor knowledge is a factor affecting low self-efficacy in nurses. Attitudes may contribute to the relationship between knowledge and self-efficacy, but these relationships have been rarely examined in nurses. Hypothesis: Attitudes moderate the relationship between knowledge and self-efficacy in palliative care among nurses, controlling for covariates. Methods: Data were collected from 282 nurses (Median age: 29 years) regarding self-efficacy, knowledge, attitudes, and covariates (i.e., age, marital status, work experience, experience of advance directive [AD] education, experience of AD with relatives, experience of AD education for patients, and experience of AD counseling). Process v4.1 for SPSS was used to test the hypothesis. Results: The levels of self-efficacy (5.9 out of 10), knowledge (14.6 out of 21), and attitudes (48.0 out of 64) among nurses were moderate. Higher levels of knowledge (p = .026) and attitudes (p &lt; .001), the interaction term of knowledge and attitudes (p = .041), and experience of AD counseling (p = .008) were significantly associated with higher levels of self-efficacy in palliative care (F = 5.643, p &lt; .001, R 2 = .172), indicating the moderating effect of attitudes. The relationships between higher levels of knowledge and higher levels of self-efficacy were significant only in nurses with highly (p = .005) and moderately positive attitudes (p = .026), but not in nurses with lack of positive attitudes (Figure 1). Conclusions: The findings of this study supported the hypothesis. To improve self-efficacy in palliative care among nurses, improvement in knowledge and facilitation of positive attitudes are needed.
Abstract 10043: Plasma Metabolite Dimethylguanidino Valeric Acid and Risk of Incident Coronary Heart Disease Among Women
Authors: Yoriko Heianza, Xuan Wang, Saumya Tiwari, Jeramie Watrous, Kathryn M Rexrode, Qi Sun, Mohit Jain, Joann E Manson, Lu Qi
Journal: Circulation (2022)

Introduction: Circulating dimethylguanidino valeric acid (DMGV) has been related to visceral adiposity and unhealthy obesogenic lifestyle factors, and recently emerged as an early marker of cardiovascular disease. Hypothesis: We tested whether circulating DMGV was associated with the risk of coronary heart disease (CHD) among women. We also investigated obesogenic diet/lifestyle factors and biomarkers associated with higher DMGV levels. Methods: This prospective nested case-control study included 1518 women (759 incident cases of fatal CHD and nonfatal myocardial infarction and 759 controls) from the Nurses’ Health Study (NHS). Incident cases of CHD were identified over 10-14 years of follow-up time. Obesogenic lifestyle factors (such as physical inactivity and dietary intakes), adiposity, and cardiometabolic abnormalities (hypertension, dyslipidemia, and diabetes) were assessed in the NHS and the Women's Lifestyle Validation Study (WLVS; n=723). Results: In the NHS, higher plasma DMGV levels were related to greater risk of CHD (P for linear relation=0.007) after controlling for demographic factors, family history of myocardial infarction, and postmenopausal hormone. Compared with women in the lowest quartile of DMGV levels, those in the highest quartile had a relative risk (RR) of 1.70 (95% CI: 1.25, 2.31) for CHD. The RR in the highest quartile was attenuated after controlling for obesogenic factors and adiposity. Obesogenic diet/lifestyle factors, adiposity, altered adipokine levels, and cardiometabolic abnormalities were significant factors related to higher plasma DMGV levels in the NHS and WLVS. Conclusions: Circulating DMGV may be a significant metabolite related to obesogenic diet quality, lifestyles, and cardiometabolic abnormalities among women. High DMGV levels were associated with an increased risk of incident CHD among women.
Abstract 10044: An Analysis of Thrombectomy Usage Among Different Hospital Types
Authors: Karan Patel, Kamil Taneja, Solomon Oak, Jared Wolfe, Pratit Patel, Michael T Mullen, James E Siegler
Journal: Circulation (2022)

Introduction: Introduction: Prior studies have shown an increase in utilization of thrombectomy in acute stroke over the past few years. However, the likelihood of a thrombectomy being performed may be different among different hospital types. Methods: Using the National Emergency Department Sample (NEDS) database, we retrospectively queried patients with acute cerebral infarction from 2006 to 2019. Patients were compared based on treatment with or without thrombectomy. Multivariable logistic regression was performed to estimate the odds of thrombectomy based on hospital characteristics to identify disparities in treatment utilization. Results: Of the 2,998,192 patients with an acute stroke, 44,548 (1.49%) had a thrombectomy. Patients treated after 2006 had significantly higher odds of having a thrombectomy, with a stepwise increase in the odds of thrombectomy for each subsequent year. After adjustment for factors such as income status, insurance type, gender, and comorbidities, we found that patients from trauma centers were more likely to undergo thrombectomy than patients admitted to non-trauma centers (Level 1 vs. non-trauma OR 3.06, 95%CI 2.37- 3.95; Level 2 vs. non-trauma OR 1.97, 95%CI 1.42-2.73). Also, patients admitted to metropolitan teaching centers were more likely to have a thrombectomy than patients admitted to non-metropolitan teaching centers (OR 2.77 95%CI 1.80-4.25). Conclusions: The varying degrees of thrombectomy usage may be due to centralized resources and multi-disciplinary care available at larger, urban centers. It could also be explained by the lack of neurointerventionalists who perform thrombectomies in community centers.
Abstract 10067: Association of Race and Education With Postpartum Cardiology and Primary Care Follow-Up Among Women With Preeclampsia
Authors: Malamo E Countouris, Kayle Shapero, Alisse Hauspurg, Gretchen Swabe, Jared W Magnani
Journal: Circulation (2022)

Introduction: Preeclampsia is associated with cardiovascular disease (CVD), and follow-up in women for CVD prevention is essential. We examined racial differences in follow-up with primary or cardiology care and assessed if social factors modified that association. Methods: We conducted our analysis in an administrative database (Optum’s de-identified Clinformatics® Data Mart) and identified women with preeclampsia diagnosed from 9/2014-9/2019. Odds of a follow-up visit with a primary care provider or cardiologist within 6 months after delivery were compared among Black versus White women using multivariable logistic regression models adjusting for age, comorbidities (by Elixhauser score), income, education, insurance type, and number of adults per household. We examined the effect modification of education and income on follow-up by race. A Cox proportional hazard model was used to compare time to follow-up. Results: Of 22,887 women with a diagnosis of preeclampsia (age 31.7±5.6 years), 2,736 (12.0%) were identified as Black race and 3440 (15.0%) Hispanic. Education, income, and comorbidities differed by race and ethnicity. Black women had lower odds of follow-up with a primary care provider or cardiologist within 6 months after delivery: adjusted odds ratio (aOR) 0.85 [95% confidence interval (CI) 0.78-0.92] compared with White women and were 13% less likely to have follow-up in adjusted time to event models. Hispanic women also had lower odds of follow-up: aOR 0.84 [95% CI 0.78-0.91] and were 12% less likely to have follow-up compared with white women. There was an effect modification of education by race on follow-up (p for interaction=0.001), but not income (p for interaction=0.14). Conclusions: Black and Hispanic women have decreased odds of follow-up with a primary care provider or cardiologist than White women in the 6 months postpartum, a disparity that may be modified by socioeconomic factors. Improving follow-up care for Black women, particularly those with less than a college-level education, may enhance CVD prevention.
Abstract 10188: Does Myocardial Contraction Fraction Predict Mortality in the Oldest Old
Authors: David Leibowitz, Yara Bishara, Jeremy Jacobs, Dan Gilon, Irit Stessman-Lande, jochanan stessman
Journal: Circulation (2022)

Background: People over the age of 85 are the world's most rapidly growing age group and have a high incidence of cardiovascular mortality. Ejection fraction (EF), the most commonly used index of systolic function, may be limited prognostically in this population given the high incidence of left ventricular hypertrophy and myocardial contraction fraction (MCF) may be more accurate. The objective of this longitudinal study was to assess the prognosis of MCF in an age-homogenous, community-dwelling population of subjects. Methods: Subjects were recruited from the Jerusalem Longitudinal Cohort Study. Echocardiography was performed with a portable echocardiograph at the subjects place of residence. Standard echocardiographic assessment of cardiac structure and function including MCF was performed. 5-year mortality was assessed via a centralized government database. Results: 418 subjects (197 males, 218 females) were enrolled in the study of whom 113 (27%) died at the time of 5-year follow-up. Subjects who died had significantly lower MCF (32 ± 14% vs. 36 ± 12%; p &lt; 0.004) and EF (51.6 ± 11.6% vs 56.3 ± 9.4%; p&lt; 0.0001) than survivors. On Kaplan-Meier analysis MCF was more significantly associated with mortality than EF (p&lt; 0.0005 vs p &lt; 0.04). The association between MCF and mortality remained significant on multivariate analysis as both a categorical and continuous variable while EF was only significant as a continous variable. Conclusions: MCF assessed by home echocardiography provides additional prognostic information to EF and may be a superior predictor of 5-year mortality in a community-dwelling population of the oldest old.
Abstract 100: Multi-drug Cocktail Approach After Asphyxial Cardiac Arrest And Cardiopulmonary Bypass Resuscitation In Rats
Authors: Rishabh C Choudhary, Muhammad Shoaib, Tai Yin, Kei Hayashida, Mingzhu He, Yousef Al-Abed, Junhwan Kim, Lance B Becker
Journal: Circulation (2022)

Background: Cardiac arrest (CA) is a leading cause of death in the US. There are limited therapies that substantially improve survival with good neurologic outcomes. The lack of neuroprotective drugs has been cited as a major roadblock to improved outcomes. There have been many failed human trials of potentially neuroprotective drugs. However, most of the failed prior studies have focused on a single drug or single pathological pathway. By contrast, our metabolomic data suggests that after CA multiple pathways are severely dysregulated. Objective: The aim of this study was to develop and test the therapeutic effectiveness of a multi-drug cocktail targeting multiple dysfunctional pathways observed during brain ischemia-reperfusion. We sought to increase survival with good neurological outcomes in a highly lethal rat model of 20 min CA followed by cardiopulmonary bypass (CPB) resuscitation. Methods: A multi-drug cocktail formulation was developed comprised of ten drugs (Metformin, poloxamer 188, N- acetylcysteine, Sulbutiamine, Zoniporide, SS-31, Cyclosporin A, CoQ10, Vitamin C, and Edaravone) focusing on distinct metabolic pathways of ischemia-reperfusion injury. Male Sprague-Dawley rats (400-500 g) underwent 20 min of asphyxial-CA and 30 min of CPB resuscitation. After the resumption of spontaneous circulation (ROSC), rats received either cocktail or a vehicle (n=6) through a femoral vein for over a 20-minute. Animals were extubated after 4 h of mechanical ventilation. Body temperature was maintained at 37.0 ± 0.5°C. Outcomes assessed include a 4 h survival time and retention of corneal reflex. Results: Cocktail treatment resulted in 4/6 rats surpassing the 4 h survival window, while only 2/6 rats after vehicle treatment. The median survival time was 240.53 min vs 120.62 min for a cocktail vs vehicle, respectively (p=0.067). Furthermore, 4/6 rats treatment with a cocktail demonstrated retention of corneal reflex after 4 h compared with 2/6 rats after vehicle treatment. Conclusion: This pilot study is the first to use a multi-drug cocktail in a severe CA rodent model that demonstrates a trend for better survival and corneal reflex retention. Future studies of cocktails seem warranted if neuroprotective therapies are contemplated in the setting of CA.
Abstract 10670: Impact of Virtual Interviewing on Geographic Placement in the Cardiology Fellowship Match
Authors: Usman A Hasnie, Ammar Hasnie, carlos estrada, Gaby WEISSMAN, Winter Williams, Steven G Lloyd
Journal: Circulation (2022)

Introduction: Virtual interviewing for cardiology fellowship was instituted in the 2021 fellowship application cycle due to the COVID-19 pandemic and restricted travel. It is unknown what impact this has had on geographic patterns of fellow-training program matching. Our aim was to determine if there was a significant difference in the geographic placement in the cardiology fellowship match based on virtual interviews compared to prior years with in-person interviewing. Methods: All U.S. based accredited cardiovascular disease fellowship programs that participated in the 2019-2021 fellowship match cycles were identified. Those that had publicly available data regarding fellow residency training and training year were included. Each fellow was categorized based on their fellowship program and residency training as from the same program, from the same state, from the same region or from a different region. These were mutually exclusive categories. Results: Of the 236 eligible programs, 118 programs (50%) had available data for the 2019-2021 application cycles. Cumulatively n=1787 total fellows were identified. Compared to the pre-virtual cohort (n=1178 matched fellows) there was no difference in the geographic placement during the 2021 virtual cycle (n=609 matched fellows) including the proportion that matched at the same program (30.6% vs 31.5%, p=0.738), in the same state (13% vs 13.8%, p=0.719), same region (24.2% vs 19.7%, p=0.164), or different region (35% vs 33.1%, p=0.274). There was also no difference when stratified by small, medium, or large program size or geographic region. Conclusions: The use of virtual interviewing in the 2021 cardiology fellowship application cycle did not result in a significant difference in the geographic placement of fellows. Further study is needed to evaluate the impact of virtual interviewing and optimize its use in fellowship recruitment.
Abstract 10184: The Risk Factors for Ischemic Sudden Cardiac Death in Women
Authors: Ida Hookana, Lauri Holmstrom, Antti Kiviniemi, Tuomas Kentta, Anette Haukilahti, Juha Vahatalo, Mikko Tulppo, Olavi Ukkola, Samuli Lepojarvi, Jani Tikkanen, Olli-Pekka Piira, Lasse Pakanen, Juha Perkiomaki, Heikki Huikuri, Juhani Junttila
Journal: Circulation (2022)

Background: Sudden cardiac death (SCD) is a significant cause of death accounting for 15-20 % of all deaths in Western countries. Coronary artery disease (CAD) is the most common cause of SCD. Even though women are at a lower risk for SCD &amp; CAD, the decline in mortality of these conditions has been slower in women than in men. Previous studies have shown that CAD is more challenging to detect in women, hence SCD is often the first manifestation of underlying CAD among women. The aim of this case-control study was to determine factors associated to SCD due to CAD in women. Methods: The study group consists of women with ischemic SCD (N=888) derived from the Fingesture study conducted in Northern Finland from 1998 to 2017 and all SCDs were autopsy verified. The control group consisted of women with angiographically verified CAD without SCD occurring during the 5-year-follow-up (N=610) from Artemis study. To perform comparison between these groups, we utilized medical records, autopsy findings, echocardiograms and ECGs. Results: Subjects with SCD were older (73.2±11.3 vs. 68.8±8.0 p &lt; 0.001) and were more likely to be smokers or ex-smokers (37.1% vs. 27.6 %, p = 0.045). The proportion of subjects with prior myocardial infarction (MI) was higher in controls (46.9 % vs. 41.4 % in SCD subjects, p = 0.037), but in contrast, SCD subjects were more likely to have underlying silent MI (25.6 % vs. 2.4 % in CAD controls, p &lt; 0.001). Decreased left ventricular ejection fraction (LVEF 35-55 %) was more common finding in SCD subjects than in CAD controls (33.1% vs. 8.7 %, p &lt; 0.001, respectively) as well as LV hypertrophy (70.9 % vs. 55.1 %, p &lt; 0.001, respectively). Various ECG-abnormalities were more common in SCD subjects including higher heart rate, prolonged QTc- and JTc-intervals, wide or fragmented QRS-complex, short PR-interval and early repolarization. The prevalence of Q-waves and T-inversions did not differ between these groups. Conclusions: Underlying CAD and MI are often underdiagnosed in women with ischemic SCD considering the high proportion of silent myocardial infarctions and the number of subjects without prior CAD diagnosis. LV hypertrophy as well as decreased LVEF were more frequent findings in SCD subjects. Several ECG abnormalities were more common among subjects with SCD.
Abstract 10766: Analysis of Cardiac Ct Anatomy in Patients With Severe Tricuspid Regurgitation Considered for Transcatheter Intervention
Authors: Brenden Ingraham, Katie Young, Prajwal Reddy, Vidhu Anand, John M Stulak, Charanjit RIHAL, Mackram F Eleid, Thomas A Foley
Journal: Circulation (2022)

Introduction: Severe tricuspid regurgitation (TR) is associated with considerable morbidity/mortality in an elderly population with multiple comorbidities. There is interest in transcatheter interventions to manage severe TR in this population. Understanding right heart (RH) anatomy has implications for patient/device selection for transcatheter intervention. Hypothesis: We analyzed RH anatomy by CT of patients referred for TR therapy to determine transcatheter tricuspid intervention device sizing needs. Methods: Retrospective Mayo Clinic study of 29 patients considered for intervention of severe TR from 3/1/2016-12/15/2020; echocardiogram and CT angiogram obtained in all patients. Results: Mean age was 83±8 (83% female), 100% had atrial fibrillation, and 62% had chronic kidney disease ≥3a. 97% were symptomatic, 93% were prescribed loop diuretics, and 24% had device leads. Mean tricuspid annular plane systolic excursion 16.8±4.5 mm, effective regurgitant orifice area (EROA) 81±33 mm 2 , and cardiac index 2.6±0.6 L/min/m 2 . 41% had at least moderate right ventricular (RV) dysfunction with a mean RV systolic pressure of 46±16 mmHg. Patients receiving intervention had significantly larger EROA (101±33 v. 63±22 mm 2 , P=0.033), shorter tricuspid leaflet tenting length (6.5±3.0 v. 8.9±2.7 mm, P=0.042), and smaller annuloplasty diagnostic perimeter during diastole (120.1±16.6 v. 131.1±7.4 mm, P=0.041). Intervention patients tended to have better right ventricular function, smaller RV and IVC size, and more severe symptoms. Max tricuspid annulus diameter in systole and diastole was 51±5 and 53±7 mm, respectively. Conclusions: Severe TR patients referred for transcatheter intervention present with severe RH enlargement with a large proportion having tricuspid annulus dimensions outside the range for current devices available in clinical trials. These data have implications for device development/selection and procedural feasibility.